Benedetti, who heads the psychiatry and clinical psychobiology unit at San Raffaele Hospital in Milan, has been investigating ‘wake therapy’, in combination with bright light exposure and even microdoses of lithium, as a means of treating depression where drugs have often failed.

His work and results have attracted the attention of psychiatrists in the USA, the UK and other European countries. They are starting to take notice, launching variations of it in their own clinics with his results as a baseline for testing.

These ‘chronotherapies’ seem to work by kick-starting a sluggish biological clock; in doing so, they’re also shedding new light on the underlying pathology of depression, and on the function of sleep more generally.

“Sleep deprivation really has opposite effects in healthy people and those with depression,” says Benedetti. If you’re healthy and you don’t sleep, you’ll feel in a bad mood. But if you’re depressed, it can prompt an immediate improvement in mood, and in cognitive abilities.

According to his research, there’s also a dangerous catch to this method: once you go to sleep and catch up on those missed hours of sleep, you’ll have a 95 per cent chance of relapse.

The Germans were actually the first to report on the antidepressant effects of sleep deprivation back in 1959. This captured the imagination of a young researcher from Tübingen in Germany, Burkhard Pflug, who investigated the effect in his doctoral thesis and in subsequent studies during the 1970s. By systematically depriving depressed people of sleep, he confirmed that spending a single night awake could jolt them out of depression.

The brain activity of people with depression looks different during sleep and wakefulness than that of healthy people. During the day, wake-promoting signals coming from the circadian system – our internal 24-hour biological clock – are thought to help us resist sleep, with these signals being replaced by sleep-promoting ones at night. Our brain cells work in cycles too, becoming increasingly excitable in response to stimuli during wakefulness, with this excitability dissipating when we sleep. But in people with depression and bipolar disorder, these fluctuations appear dampened or absent.

One theory to explain this is that depressed people simply need added sleep pressure to jump-start a sluggish system. Sleep pressure – our urge to sleep – is thought to arise because of the gradual release of adenosine in the brain. It builds up throughout the day and attaches to adenosine receptors on neurons, making us feel drowsy. Drugs that trigger these receptors have the same effect, whereas drugs that block them – such as caffeine – make us feel more awake.

Bright light, meanwhile, is known to alter the rhythms of the suprachiasmatic nucleus, as well as boosting activity in emotion-processing areas of the brain more directly. Indeed, the American Psychiatric Association states that light therapy is as effective as most antidepressants in treating non-seasonal depression.

Despite the promising results against bipolar disorder, wake therapy has been slow to catch on in other countries. “You could be cynical and say it’s because you can’t patent it,” says David Veale, a consultant psychiatrist at the South London and Maudsley NHS Foundation Trust.

The bias towards pharmaceutical solutions has kept chronotherapy below the radar for many psychiatrists. “A lot of people just don’t know about it,” says Veale.